tbuckley/cabot-search huggingface dataset:
Use of IsoPSA with prostate MRI PIRADS score in biopsy decision making in patients with elevated PSA.
Authors: Tarik Benidir, Zaeem M Lone, Nour Abdallah, Andrew Wood, Rebecca Campbell, Andrei Purysko, Jane Nguyen, Eric A. Klein, Robert Abouassaly, Steven Campbell, Christopher J. Weight
Journal: Journal of Clinical Oncology (2023)

388 Background: IsoPSA is prospectively validated to be superior to PSA and percent free PSA in predicting prostate cancer (PCa) as well as clinically significant prostate cancer. We sought to evaluate the use of IsoPSA in combination with prostate magnetic resonance imaging (MRI) and the prostate imaging reporting and data systems (PIRADS) on predicting either benign/indolent or csPCA at biopsy. Methods: This was a single center retrospective review of prospectively collected patient data that included all patients who underwent IsoPSA testing, preoperative prostate MRI and prostate biopsy from 2019-2021. Chi Squared analysis was used to assess for associations between a binary classification of low (&lt;6) or elevated (&gt;6) IsoPSA index, in combination with PIRADS scores in predicting either indolent/benign or csPCa at biopsy. Logistic regression was used to explore independent predictors of csPCa. Receiver Operating Curve (ROC) analysis was completed with areas under the curve (AUC) for IsoPSA and PIRADS scores, both alone and in combination. Predictive probabilities were assessed using combinations of IsoPSA thresholds and PIRADS scores. Results: 207 patients met inclusion criteria. Among patients with a negative MRI, low IsoPSA index was associated with a lower chance of csPCa compared to those with elevated IsoPSA (2% vs 15%, p&lt;0.018). For those with a PIRADS 4-5 lesion, elevated IsoPSA index was associated with a higher chance of csPCa at biopsy compared to a low IsoPSA index (49% vs 19%, p=0.05). On multivariate analysis, elevated IsoPSA and PIRADS 4-5 were independent predictors of csPCa (p&lt;0.001). Similarly, low IsoPSA index and negative MRI were independent predictors of benign/indolent disease at biopsy (p&lt;0.001). Using predictive probabilities, the combination of PIRADS 4-5 with elevated IsoPSA was associated with the highest risk of csPCa (48%) and the highest AUC (0.83) for predicting csPCa. This AUC value was superior to either marker alone (0.76, 0.76) and total PSA alone (0.57) (p&lt;0.001). Conclusions: The combination of elevated IsoPSA with adverse PIRADS score (4-5) is associated with a 48% predicted probability of csPCa at biopsy with an AUC of 0.83, which was more accurate than either marker alone. A low IsoPSA in combination with a negative MRI resulted in a 98% chance of benign/indolent disease at biopsy. These findings may prove useful for the practicing Urologist and may help guide discussions regarding the need for biopsy when interpreting various IsoPSA/PIRADS combinations. [Table: see text]
A retrospective review of the benefits vs. safety implications of prednisolone during docetaxel chemotherapy alongside androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC).
Authors: Molly Jameson, Claire Barker, Jennifer King, Hui-Wen Liang, Charles Carey, Nicole Cripps, Daisy Jameson, Kamlesh Patel, Andrew Robinson, Andrew Hudson, Yee Pei Song, Ruth Conroy, Maria Serra, Ananya Choudhury, John Logue, James Wylie, Anna Tran
Journal: Journal of Clinical Oncology (2023)

132 Background: A key difference between the landmark trials for docetaxel chemotherapy alongside ADT for mHSPC was the addition of prednisolone in the STAMPEDE but not CHAARTED or GETUG-AFU 15 trials, resulting in varied use in clinical practice. Potential toxicity from prolonged steroid use was recognised in a 2020 NHS England safety alert. This retrospective study compared toxicities in patients treated with docetaxel +/- prednisolone. Methods: Electronic notes of patients treated with docetaxel and ADT +/- prednisolone (per consultant preference) Feb 2018 - Sept 2020, were reviewed. Data was collected on common toxicities using CTCAE v5 grading. Analysis of incidence and severity were carried out using paired T-tests and logistic regression due to small sample sizes at each severity grade. Results: Data on 299 patients was collected; 167 received docetaxel and ADT, 132 also received prednisolone. There was no significant difference in the number of cycles completed between the 2 groups; 66.5% (no prednisolone) v 70.4% (with prednisolone) of patients completed 6 cycles (p=0.41). There was a significant difference in both the incidence and severity of anaemia between patients treated +/- prednisolone. There was no significant difference in the incidence of neutropenia or alopecia between patients treated +/- prednisolone, but prednisolone use was predictive of lower severity scores in neutropenia and alopecia. In contrast, there was a significant difference seen in incidence of neuropathy between the 2 groups, with no impact on severity. There was no significant difference in incidence or severity of thrombocytopenia, neutropenic sepsis, fatigue or nausea/vomiting. The prednisolone group had a significant increase in contacts with an advice hotline or general practitioner (p values &lt;0.001). Review of interactions found many were requesting support with administration of prednisolone. Conclusions: These findings suggest limited clinical benefit in the addition of prednisolone to docetaxel and ADT in patients with mHSPC. Prednisolone is associated with significant potential harms e.g., impaired blood glucose and adrenal insufficiency (blood glucose was not routinely recorded in this group). These preliminary findings would benefit from further study with a larger sample size. [Table: see text]
Long-term rates of biochemical recurrence after primary external beam radiation therapy (EBRT) for prostate cancer.
Authors: Domenique Escobar, Lufan Wang, Jasmin Banton, Janet E. Cowan, Samuel L. Washington, Osama Mohamad, Mani Menon, Peter Carroll
Journal: Journal of Clinical Oncology (2023)

393 Background: Radiation therapy is a common form of treatment for men with prostate cancer. Biochemical recurrence (BCR) is most commonly defined using the Phoenix definition of PSA nadir + 2. We sought to characterize long term rates of biochemical recurrence in a large, well-characterized and well-followed cohort of men treated with primary EBRT. Methods: Patients enrolled in CaPSURE, a national registry of men diagnosed with prostate cancer, from 1995 - 2017 with clinically localized prostate cancer (cN0M0/X, PSA&lt;=50) treated with primary EBRT were included. Cancer risk was defined by NCCN criteria. Cox proportional hazards regressions were used to assess associations between patient characteristics and BCR as defined by PSA nadir + 2. Results: 1193 patients were included. Mean age at diagnosis was 70 (SD 6.82), median PSA at diagnosis was 7.6 and mean number of follow up PSA tests was 5. Overall rates of BCR were 17.4% at 5 years and 39.4% at 10 years. Rates of BCR were significantly associated with NCCN risk with high-risk patients having the highest rates of recurrence, followed by intermediate- and low-risk groups (61.5%, 36.4% and 28.5% respectively at 10 years). NCCN high vs low clinical risk was significantly associated with likelihood of BCR (HR 4.8, CI 2.5 – 9.2). Rates of salvage treatment, usually ADT, were 16% at 5 years and 19% at 10 years and these were also significantly associated with NCCN high vs low clinical risk (HR 3.7, CI 2.3 – 6) and concurrent ADT (HR 1.83, CI 1.2 – 2.7). Overall rates of bone metastases were 2.6% at 5 years and 4% at 10 years. Overall prostate cancer specific mortality was 3% at 5 years and 7% at 10 years. Conclusions: In this analysis, rates of BCR were fairly high and consistent with published RTOG studies, but rates of salvage treatment were relatively low in comparison, indicating that not all patients who recur need, are offered or want treatment. The limitations of this analysis include incomplete information on radiation dose and field size. The strengths of this analysis include the size of the cohort and the length of follow-up. Furthermore, as this cohort largely represents treatment in community settings, the results may be broadly applicable.
Association of obesity with tumor differential gene expression and gene set enrichment pathways in advanced prostate adenocarcinoma (PCa).
Authors: Vinay Mathew Thomas, Beverly Chigarira, Georges Gebrael, Nicolas Sayegh, Nishita Tripathi, Yeonjung Jo, Roberto Nussenzveig, Kamal Kant Kant Sahu, Haoran Li, Clara Tandar, Divyam Goel, Taylor Ryan McFarland, James Brundage, Benjamin L. Maughan, Umang Swami, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2023)

231 Background: Increased Body Mass Index (BMI) has been linked to increased prostate cancer incidence, recurrence, and mortality (PMID: 35538398). Herein, we sought to investigate the underlying differences in gene expression profiles based on BMI in patients (pts) with PCa. Methods: In this IRB-approved retrospective study, eligibility criteria included histologically confirmed PCa and available RNA sequencing results from treatment naïve primary prostate tissue by a CLIA-certified lab. Pts were categorized into two cohorts: obese (Ob, BMI≥30) and non-obese (non-Ob, BMI&lt;30). BMI at the time of diagnosis of PCa was used for analysis. The DEseq2 pipeline was used to analyze differentially expressed genes between the groups. The data included the Log2 fold change, Wald-Test p-values, and Benjamini-Hochberg adjusted p-values (q values) for each differentially expressed gene. These results were subjected to Gene Set Enrichment software analysis (GSEA) to identify pathways enriched in each cohort. All bioinformatic analysis was undertaken using R v4.2. Results: 60 pts were eligible, of which 22 were Ob and 38 were non-Ob. Tumor tissues from Ob pts had an increased expression of the heme metabolism, androgen-response, protein secretion, fatty acid, and bile metabolism pathways. Non-Ob pts had a significantly higher expression of genes involved in the inflammation pathways (interferon-alpha &amp; TNF alpha pathways). Normalized enrichment scores are reported. Differential individual gene expression profiles will be presented at the meeting. Conclusions: Our study showed upregulation of distinct genomic pathways in Ob pts with prostate cancer which may help personalize medicine and guide further drug development. These hypothesis-generating data require external validation. [Table: see text]
National population-based survival estimates after definitive radiation therapy for prostate cancer.
Authors: Daniel Herr, David Elliott, Kristian Stensland, Megan Veresh Caram, Jennifer Burns, Brent Hollenbeck, Jordan Sparks, Chris Shin, Alexander Zaslavsky, Alexander Tsodikov, Ted Skolarus
Journal: Journal of Clinical Oncology (2023)

395 Background: Understanding contemporary radiation therapy outcomes for prostate cancer (i.e., metastasis, death) is important for shared decision-making and setting expectations for patients and providers. Unfortunately, long-term outcome estimates are often derived from meta-analyses of outdated prospective clinical trials or population-based data lacking reliable clinical details (e.g., incident metastatic disease). For these reasons, we used a recently validated, natural language processing algorithm to identify incident metastatic prostate cancer within the electronic medical records of men treated with radiation therapy for localized prostate cancer in order to conduct an innovative and contemporary population-based survival outcomes study. Methods: We used national administrative, cancer registry, and electronic health record data for patients undergoing definitive radiation therapy with or without concurrent androgen deprivation therapy (ADT) within the Veterans Health Administration from 2005 to 2015. We used National Death Index data through 2019 for overall and prostate cancer-specific survival, and identified the date of incident metastatic prostate cancer using a validated natural language processing algorithm. We estimated metastasis-free, prostate cancer-specific, and overall survival using Kaplan-Meier methods. Results: We identified 41,876 patients treated with definitive radiation therapy for prostate cancer from 2005 through 2015, and followed them for over 8 years (follow up, median, 8.7 years, age at diagnosis, median, 65 years). Most patients had intermediate (42%) and high risk (33%) disease, with nearly half treated with ADT as part of initial therapy (44%). Unadjusted 10-year metastasis-free survival was 96%, 92%, and 80% for low, intermediate, and high risk disease. Similarly, unadjusted 10-year prostate cancer-specific survival was 98%, 97%, and 90% for low, intermediate, and high risk disease. Unadjusted overall survival was lower across disease risk categories at 77%, 71%, and 62% for low, intermediate, and high risk disease. Conclusions: These data provide population-based benchmarks for clinically relevant endpoints, including metastasis-free survival, among patients with low, intermediate, and high risk prostate cancer undergoing radiation therapy using contemporary techniques. The survival rates for high risk disease, in particular, compare favorably with historical outcomes.
Activity of lutetium-177 PSMA (Lu-PSMA) and determinants of outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with cabazitaxel: The PACAP study.
Authors: Ronan Flippot, Tugce Telli, Maud Velev, Aude Flechon, Lea Turpin, Andre M. Bergman, Fabio Turco, Wolfgang Peter Fendler, Anne Laure Giraudet, Françoise Montravers, Wouter V. Vogel, Silke Gillessen, Simona Berardi, Ken Herrmann, David Kryza, Gaetano Paone, Camilo Garcia, Stéphanie Foulon, Arnaud Pages, Karim Fizazi
Journal: Journal of Clinical Oncology (2023)

180 Background: Cabazitaxel and Lu-PSMA both improved survival in patients with mCRPC after docetaxel and an androgen receptor pathway inhibitor (ARPI), but there is limited data regarding Lu-PSMA activity after cabazitaxel. We aimed at assessing activity of Lu-PSMA and determinants of outcomes in this setting. Methods: Consecutive mCRPC patients from 6 European centers treated with Lu-PSMA after cabazitaxel were included in this retrospective study. Endpoints included radiographic progression-free survival (rPFS), time to PSA progression (PSA-TTP), PSA decline, objective response, overall survival, and safety. Results: Of 101 patients included (median age 67y), 64% had ISUP grade 4-5 disease; 71% had bone +/- nodal (LN) metastases, 22% visceral metastases, 7% LN only. All patients and 92% had received previous docetaxel and a prior ARPI (≥ 2 in 47%) before cabazitaxel respectively. Patients had received a median number of 6 cabazitaxel cycles (range 1-26). DNA damage repair alterations (DDR) were found in 11/48 (23%) patients with available testing. Patients received a median number of 3 Lu-PSMA cycles (range 1-14). With a median follow-up of 5.7 months, the median rPFS from Lu-PSMA initiation was 4.3 months (m, 95%CI 3.2-5.7) and median PSA-TTP was 3.5 m (95%CI 3.0-4.5). Overall, 44 patients (44%) experienced a PSA decline ≥ 50% (PSA50), 54 (53%) ≥ 30% (PSA30), and 67 (66%) any PSA decline. Objective response rate was 34%. Baseline characteristics associated with shorter rPFS on Lu-PSMA included ISUP grade 4-5 disease (median rPFS of 3.5 vs. 7.2m, p=0.02) and a time to castration resistance &lt; 12 months (3.1m vs. 4.5m, p=0.04). Patients with LN only had longer rPFS compared to those with bone and visceral metastases (median NR vs. 3.6 and 3.7m, respectively, p=0.02). There was no association between activity of Lu-PSMA and DNA damage repair alterations, duration of previous cabazitaxel therapy, and number of previous ARPI. During Lu-PSMA, a profound PSA decline was associated with longer rPFS: patients achieving PSA50, PSA30 or any PSA decline had respective median rPFS rates of 9.0, 8.3 and 6.2 months, while those who did not experience any PSA decline had a median rPFS of only 2.6 months. Conclusions: Lu-PSMA demonstrated substantial PSA decline but limited duration of response after cabazitaxel in a real-life setting. Adverse baseline characteristics and absence of PSA decline may help early identification of poor responders.
Enfortumab vedotin (EV) alone or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer (la/mUC): Subgroup analyses of confirmed objective response rate (cORR) from EV-103 cohort K.
Authors: Peter H. O'Donnell, Jonathan E. Rosenberg, Christopher J. Hoimes, Daniel P. Petrylak, Matthew I. Milowsky, Rana R. McKay, Sandy Srinivas, Terence W. Friedlander, Chethan Ramamurthy, Mehmet Asim Bilen, Earle F Burgess, Nataliya Mar, Helen Moon, Daniel M. Geynisman, Saby George, Anne-Sophie Carret, Yao Yu, Maria Guseva, Blanca Homet Moreno, Thomas W. Flaig
Journal: Journal of Clinical Oncology (2023)

499 Background: In EV-103 Cohort K (NCT03288545), EV and P in combination (EV+P) showed encouraging antitumor activity and a manageable safety profile when used as 1L therapy in patients (pts) w/ la/mUC who are ineligible for cisplatin, a population w/ high unmet need. Here we report results of an analysis of prespecified Cohort K subgroups known to be associated w/ poor outcomes. Methods: Pts who are cisplatin-ineligible w/ previously untreated la/mUC were randomized 1:1 to EV (1.25 mg/kg) as monotherapy on Days 1 and 8 or in combination w/ P (200 mg) on Day 1 of 3-week cycles. Primary endpoint is cORR per RECIST v1.1 by blinded independent central review w/ no formal statistical comparison between arms. Secondary endpoints included duration of response and safety (e.g. treatment-related adverse events, TRAEs). The cORR analysis was performed in prespecified subgroups including age, ECOG PS, liver metastasis, PD-L1 expression status, metastatic disease site at baseline, and primary disease site of origin. Results: 149 pts were treated: EV+P n=76; EV n=73; cORRs across key subgroups for both EV+P and EV monotherapy are shown in the table. For EV+P overall cohort, cORR (95%CI): 64.5% (52.7, 75.1); median DOR was not reached. cORRs were consistent across subgroups for EV+P including those w/ ECOG PS score of 1-2: 62.8% (46.7, 77.0) and presence of liver metastasis: 53.8% (25.1, 80.8). Among TRAEs of special interest in the EV+P arm, skin reactions occurred in n=51 (67.1%); peripheral neuropathy occurred in n=46 (60.5%). For EV+P, 68.4% of pts had TRAEs leading to interruption of either EV or P; 48.7% of pts had TRAEs leading to EV dose reduction. Median duration of EV+P treatment was 11 cycles. Conclusions: EV+P showed promising cORR in 1L cisplatin-ineligible pts w/ la/mUC; activity was consistently observed across a range of pre-specified subgroups including those with poor prognosis. EV+P TRAEs were manageable w/ close monitoring and appropriate dose modifications w/ a meaningful duration of treatment. EV+P has the potential to address high unmet needs in 1L la/mUC and MIBC and is being further evaluated in 3 Phase 3 trials (NCT04223856, NCT04700124, NCT03924895). Clinical trial information: NCT03288545 . [Table: see text]
The difference in serum testosterone recovery between Gn-RH Antagonist and LH-RH agonist among patients with prostate cancer treated with radiation therapy.
Authors: Akinori Takei, Shinichi Sakamoto, Jun Niino, Nobuyoshi Takeuchi, Manato Kanesaka, Tomokazu Sazuka, Yusuke Imamura, Koichiro Akakura, Tomohiko Ichikawa
Journal: Journal of Clinical Oncology (2023)

382 Background: Only limited data exist related to the serum testosterone (TST) recovery after discontinuation of Gn-RH antagonist (Degarelix acetate). In the present study, we investigated the difference in serum testosterone (TST) recovery between LH-RH agonist and Gn-RH antagonist among prostate cancer (Pca) patients received radiation therapy in combination with androgen deprivation therapy (ADT). Methods: We analyzed the association between TST levels after the end of endocrine therapy and clinical factors in 130 patients who underwent ADT for prostate cancer at Chiba University hospital between May 2003 and May 2020. The proportional hazards model and Kaplan-Meier methods were used for the statistical analysis. Results: The median patient age and PSA were 72 years, and 16.8ng/mL, respectively. The median initial TST and nadir TST were 457 ng/dL, and 20ng/dL, respectively. The median duration of ADT was 857 days. As factors affect the speed of recovery to the castration level (TST 50 ng/dL), univariate analysis showed that Gn-RH antagonist presented the significantly shorter TST recovery compared to those of LH-RH agonist (HR 1.9, p=0.0078), together with the duration of hormone therapy (857 days) and Nadir TST level (20 ng/dL), GS8 and PSA (16.8ng/mL). Multivariate analysis showed that Nadir TST level was an independent predictor (HR 2.0, p=0.0093). As factors affect the speed of recovery to the physiological level (TST 200 ng/dL), univariate analysis showed that Gn-RH antagonist presented the significantly shorter TST recovery compared to those of LH-RH agonist (HR 2.1, p=0.0064). Multivariate analysis showed that duration was the only independent predictor (HR0.34, p=0.0029). Kaplan-Meier curve demonstrated shorter time for the TST recovery in Gn-RH antagonist compared to the LH-RH agonist for the castration level (p=0.0064) and the physiological level (p=0.0052). Conclusions: TST recoveries were significantly shorter in Pca patients treated with Gn-RH antagonist than LH-RH agonist. Nadir TST value, duration, and a type of LH-RH drug may comprehensively suggest us the dynamics of TST recovery after ADT. [Table: see text]